Contact of Hageman factor (blood clotting factor XII) with negatively charged surfaces in the presence of prekallikrein and kininogen leads to activation of Hageman factor and generation of kallikrein. The latter enzyme converts plasminogen to the fibrin hydrolyzing enzyme plasmin. We are characterizing the kallikrein fibrinolytic pathway to allow evaluation of its possible significance in comparison to several other fibrinolytic pathways, including those mediated by plasminogen activators recovered from post-exercise plasma and from vascular tissue. We observe that bovine kallikrein causes enzymatic cleavage of plasminogen to plasmin and displays a specific activity of approximately 21 CTA units/mg of kallikrein. In contrast, we observe that the plasminogen activators from post-exercise plasma and from human vein display very high specific activities toward plasminogen comparable to urokinase (approximately 200,000 CTA units/mg). The low specific activity of kallikrein toward plasminogen appears to suggest that it may not represent a major fibrinolytic pathway. However, this tentative conclusion will require revision if blood plasma is found to contain a potent cofactor for the action of kallikrein on plasminogen. We are presently examining this possibility. Similarly we have observed that several other blood clotting enzymes activate plasminogen slowly and are examining the effect of cofactors on these reactions to evaluate their possible significance.